title: ICAM-1 deficiency exacerbates sarcoid-like granulomatosis induced by Propionibacterium acnes through impaired IL-10 production by regulatory T cells.
abstract: Propionibacterium acnes has been implicated as one of the suggested causative antigens for sarcoidosis, a systemic granulomatous disease. By injecting heat-killed P. acnes into the dorsal skin of C57BL/6J mice on days 1, 3, 5, and 14, sarcoid-like granulomatosis was induced in skin and lungs of these mice on day 28. To clarify the role of cell adhesion molecules in cutaneous sarcoidosis, we induced sarcoid-like granulomatosis in mice deficient of intercellular adhesion molecule (ICAM)-1, L-selectin, P-selectin, or E-selectin via repeated P. acnes injection. Histopathologic analysis revealed that granuloma formation was aggravated in the skin and lungs of ICAM-1-deficient mice compared with wild-type mice. Within skin granulomas of ICAM-1-deficient mice, P. acnes immunization up-regulated mRNA expression of tumor necrosis factor-α, although it failed to induce IL-10 mRNA expression in contrast to wild-type mice. Infiltration of regulatory T cells into skin granuloma was similar between wild-type mice and ICAM-1-deficient mice. P. acnes immunization induced IL-10 production by CD4(+)CD25(+)Foxp3(+) regulatory T cells in lymph nodes of wild-type mice in vivo, which was absent in regulatory T cells of ICAM-1-deficient mice. Our results indicate that ICAM-1 is imperative for inducing regulatory T cells to produce IL-10 in vivo, which would prevent granuloma formation.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kamata
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. Electronic address: ytada-tky@umin.ac.jp.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Mitsui
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyagaki
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Asano
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugaya
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kadono
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. Electronic address: satos-der@h.u-tokyo.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D015769:Granuloma, Respiratory Tract / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011425:Propionibacterium acnes / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017192:Skin Diseases, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: C556062:IL10 protein, mouse; C090509:Icam1 protein, mouse; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10